ClinVar Miner

Submissions for variant NM_001199107.2(TBC1D24):c.1321C>T (p.Arg441Cys)

gnomAD frequency: 0.00001  dbSNP: rs775497984
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000804069 SCV000943963 uncertain significance Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 2024-10-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 441 of the TBC1D24 protein (p.Arg441Cys). This variant is present in population databases (rs775497984, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with TBC1D24-related conditions. ClinVar contains an entry for this variant (Variation ID: 649192). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt TBC1D24 protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratoire Génétique Moléculaire, CHRU TOURS RCV001542063 SCV001760722 likely pathogenic not provided 2021-04-01 criteria provided, single submitter clinical testing
GeneDx RCV001542063 SCV002002451 uncertain significance not provided 2022-04-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002381761 SCV002693277 uncertain significance Inborn genetic diseases 2018-04-06 criteria provided, single submitter clinical testing The p.R441C variant (also known as c.1321C>T), located in coding exon 6 of the TBC1D24 gene, results from a C to T substitution at nucleotide position 1321. The arginine at codon 441 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Institute of Rare Diseases, West China Hospital, Sichuan University RCV005052819 SCV005687471 likely pathogenic Autosomal recessive nonsyndromic hearing loss 86 2025-01-09 criteria provided, single submitter research

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